Negative mood, depressive symptoms, and major depressive episodes (MDEs) were examined in 179 smokers with a history of major depression in a trial comparing standard smoking cessation treatment to treatment incorporating cognitive-behavioral therapy for depression (CBT-D). Early lapses were associated with relatively large increases in negative mood on quit date. Mood improved in the 2 weeks after quit date among those returning to regular smoking but not among those smoking moderately. Continuous abstinence was associated with short- and long-term reductions in depressive symptoms. MDE incidence during follow-up was 15.3% and was not associated with abstinence. Unexpected was that CBT-D was associated with greater negative mood and depressive symptoms and increased MDE risk. Results suggest complex bidirectional associations between affect and smoking outcomes.